Method and compositions for the treatment and detection of endothelin-1 related kidney diseases

Abstract

The present application relates to methods of treating HIV-associated nephropathy (HIVAN) and/or focal segmental glomerulosclerosis (FSGS) using endothelin-1 (ET-1) antagonists. The application further relates to a composition for the treatment of HIVAN and/or FSGS. A kit for detecting the presence of ET-1 or ET-1-associated biomarker in a biological sample is also disclosed.

What is claimed is: 
     
       1. A method of treating HIV-associated nephropathy (HIVAN), comprising administering to a mammalian subject with HIVAN an effective amount of a composition comprising an ET-1 antagonist selected from the group consisting of sitaxentan, ambrisentan, atrasentan, BQ-123, bosentan and tezosentan,
 wherein the subject has an increased level of ET-1 compared to an HIV positive control subject, and 
 wherein the subject has a plasma ET-1 level of greater than 4 pg/ml. 
 
     
     
       2. The method of  claim 1 , wherein the ET-1 antagonist is administered by a local infusion into a kidney of the subject. 
     
     
       3. The method of  claim 2 , wherein the ET-1 antagonist is infused through a retrograde catheter into the pyelic cavity. 
     
     
       4. The method of  claim 1 , wherein the ET-1 antagonist is administered by a close-circuit perfusion into a kidney of the subject. 
     
     
       5. The method of  claim 4 , wherein the close-circuit perfusion is performed for a range of 10-60 minutes. 
     
     
       6. The method of  claim 1 , wherein the mammalian subject is a human subject. 
     
     
       7. The method of  claim 1 , wherein the subject does not have diabetes. 
     
     
       8. The method of  claim 1 , wherein the subject is further administered an ACE inhibitor. 
     
     
       9. The method of  claim 8 , wherein the subject is administered a composition consisting of two active agents, an ET-1 antagonist and an angiotensin-converting enzyme (ACE) inhibitor. 
     
     
       10. The method of  claim 8 , wherein the ACE inhibitor is selected from the group consisting of enalapril, ramipril, quinapril, perindopril, lisinopril, benazepril, imidapril, and zofenopril.